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Cited by 6Thyroid Disorders and TreatmentsThyroid and Parathyroid SurgeryPharmacovigilance and Adverse Drug Reactions

A review of the safety of triiodothyronine in combination with levothyroxine for the management of hypothyroidism

Open access
Gottwald-Hostalek, Ulrike, Tayrouz, Yorki·2024·Current Medical Research and Opinion
DOI 10.1080/03007995.2024.2435460
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Abstract

There remains considerable interest in the therapeutic use of combinations of levothyroxine (LT4) and triiodothyronine (liothyronine, T3) in the management of hypothyroidism, especially where hypothyroid-like symptoms persist on optimised LT4 monotherapy. This interest appears to be increasing, despite the lack of consistent identification of clinical benefit in people with hypothyroidism in randomised trials going back two decades. Guidelines support an individualised trial of addition of T3 to LT4 for symptomatic patients on optimised LT4. A new generation of clinical trials seeks to address this issue, using thyroid-specific instruments to measure patient-reported outcomes, among other innovations. Safety is the other critical element of the therapeutic profile of a drug. In this article, we review the safety of treatment LT4 + T3, with an emphasis on side-effects suggestive of thyrotoxicosis (overtreatment with thyroid hormones). Randomised trials that evaluated LT4 + T3 did not raise clear or consistent safety issues with this treatment. This was despite the use of regimens with a lower ratio of LT4:T3 (usually 4-10:1) than recommended currently by clinical experts in the field. In addition, a real-world analysis of side-effects of a commercial LT4 + T3 treatment (LT4:T3 ratio 5:1) that were reported spontaneously to a pharmacovigilance database revealed a low rate of reports, both overall and with regard to symptoms possible reminiscent of thyrotoxicosis. Safety concerns regarding the possibility of iatrogenic thyrotoxicosis appear unlikely to limit the future guideline-driven therapeutic use of LT4:T3 combinations with a ratio of these ingredients of around 15:1.

AI snapshot

Written from the paper’s full text.

TL;DR

This narrative review and real-world pharmacovigilance analysis found no clear or consistent safety signal for levothyroxine plus triiodothyronine (LT4+T3) combination therapy, including thyrotoxicosis-like adverse events, despite LT4:T3 ratios lower than current expert recommendations. The authors conclude that safety concerns appear unlikely to limit guideline-driven use of LT4:T3 combinations at a ratio of around 15:1.

Key findings

  • Across randomized trials summarized with LT4:T3 ratios from 4:1 to 15:1, there were no clear or consistent safety issues; few thyrotoxicosis-like adverse events occurred mainly at very low ratios (4:1), including biochemical evidence of increased bone resorption or palpitations, and some studies noted small heart-rate increases of a few bpm.
  • A cited meta-analysis reported that “Overall, incidence of [AE] with combined therapy did not appear to differ when compared with monotherapy,” and withdrawals for thyrotoxicosis-like adverse events were about half those for symptoms reminiscent of unaddressed hypothyroidism (18 vs. 32).
  • In the real-world spontaneous AE analysis of a commercial LT4+T3 tablet (LT4:T3 ratio 5:1) from eight countries, 1,061,502,158 single units were sold from Jan 2009 to July 2024; the number of units sold per AE possibly relevant to thyrotoxicosis ranged from about 2.8 million to about 178 million, and supraventricular arrhythmias accounted for 27 reports, or one per 39,314,895 units.
  • A large retrospective observational study followed 400 individuals who had ever taken T3 and 33,955 who had taken LT4 but not T3 for an average of 17 years; there was no increased risk of cardiovascular disease, atrial fibrillation, fractures, or bisphosphonate use, but T3 use was associated with an approximately 2-fold increase in antipsychotic prescriptions and lower mean TSH (1.1 vs. 2.1 mIU/L).

Methods

  • Narrative review based on a PubMed search for triiodothyronine/liothyronine/T3 and levothyroxine/thyroxine/LT4 terms, limited to clinical trial, randomized clinical trial, meta-analysis, systematic review, or observational study; only adults with primary hypothyroidism were considered, with preference given to meta-analyses/systematic reviews and RCTs, followed by larger and/or prospective observational studies.
  • Novel analysis of spontaneously reported adverse events for a commercial LT4+T3 combination tablet (Euthyral VR or Novothyral VR; LT4:T3 ratio 5:1; tablet strengths 100 mcg/20 mcg or 75 mcg/15 mcg) using the Merck Global Pharmacovigilance database, with events grouped by MedDRA system organ class and descriptive statistics used without significance testing.
  • Sales data for the medication in countries that submitted AE reports and had market information available were used to contextualize reporting rates from Jan 2009 to July 2024 inclusive.

Limitations

  • The paper states that this is a narrative rather than systematic review; the clinical evidence base is heterogeneous, especially for safety outcomes, which were not given the same priority as efficacy findings in most publications reviewed; synthesis is also limited by lack of consensus on optimal trial designs, patient populations, and the optimal LT4:T3 ratio.
  • The paper states that the real-world evaluation was retrospective, uncontrolled, and based on spontaneous AE reports, which give no information on incidence or prevalence; underreporting, limited details in submissions, uncertain causality, and availability of data from only some countries were potential sources of bias.
  • Evident from the text: both authors are employees of Merck Healthcare KGaA, which funded the article and provided the pharmacovigilance data; this sponsorship and conflict of interest is not listed among the review’s stated limitations.

Model-written summary. Check it against the paper before relying on it.

Integrity signals

Registry

Crossref · 10.1080/03007995.2024.2435460

Cites

62 of 62 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

0 of 54 cited sources checked · 0 supported · 0 flagged

  • Findingown data

    Randomised trials that evaluated LT4+T3 did not raise clear or consistent safety issues with this treatment.

    “Randomised trials that evaluated LT4 þ T3 did not raise clear or consistent safety issues with this treatment.”
    • Also stated in: § Future prospects · boosted
      “In terms of safety, the studies reviewed here, and the real world analysis we present above, did not raise clear or consistent issues regarding the appearance of AE reminiscent of thyrotoxicosis.”
    Quote in the paperSubstantial claim
  • Findingnone given

    The randomised trials used LT4:T3 ratios usually 4-10:1, lower than currently recommended by clinical experts.

    “This was despite the use of regimens with a lower ratio of LT4:T3 (usually 4-10:1) than recommended currently by clinical experts in the field.”
    • Also stated in: § Future prospects · plain
      “This was so despite the common use of relatively low ratios of LT4:T3, compared with current recommendations”
    Quote in the paperSubstantial claim
  • Findingcitation

    A real-world analysis of spontaneously reported side-effects of a commercial LT4+T3 treatment (LT4:T3 ratio 5:1) revealed a low rate of reports, both overall and for symptoms possibly reminiscent of thyrotoxicosis.

    “In addition, a real-world analysis of side-effects of a commercial LT4 þ T3 treatment (LT4:T3 ratio 5:1) that were reported spontaneously to a pharmacovigilance database revealed a low rate of reports, both overall and with regard to symptoms possible reminiscent of thyrotoxicosis.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: The number of packs of the T3-T4 combination tablet sold is a valid proxy for patient exposure to the medication.
  • Findingown data

    The number of single units sold to generate a single AE possibly relevant to thyrotoxicosis ranged from about 2.8 million to about 178 million.

    “The number of single units sold to generate a single AE possibly relevant to thyrotoxicosis ranged from about 2.8 million to about 178 million (Table 3).”
    Quote in the paperSubstantial claim
    • Rests on an assumption: The number of packs of the T3-T4 combination tablet sold is a valid proxy for patient exposure to the medication.
  • Findingnone given

    The regimens used in the reviewed clinical literature had a lower ratio of LT4:T3 than currently recommended by clinical experts.

    “This was despite the use of regimens with a lower ratio of LT4:T3 than recommended currently by clinical experts on the field.”
    Quote in the paperSubstantial claim
  • May combine two claims. 27
  • Classified as probably not a substantial claim. 11

  • May combine two claims.

    Findingown data

    The numbers of AE were low in each case, despite a relatively high patient exposure, especially considering the total number of single units of the T3-LT4 combination sold in these countries (1,061,502,158) during Jan 2009 to July 2024.

    “The numbers of AE were low in each case, despite a relatively high patient exposure, especially considering the total number of single units of the T3-LT4 combination sold in these countries (1,061,502,158) during the time period in which the AE were collected (Jan 2009 to July 2024, see Methods).”
    Quote in the paperSubstantial claim
    • Rests on an assumption: The number of packs of the T3-T4 combination tablet sold is a valid proxy for patient exposure to the medication.

  • May combine two claims.

    Findingcitation

    There were few suggestions of AE consistent with iatrogenic thyrotoxicosis due to overtreatment with T3, and these (biochemical evidence of increased bone resorption or palpitations) arose in studies where the LT4:T3 ratio was particularly low (4:1).

    “There were few suggestions of AE consistent with iatrogenic thyrotoxicosis due to over treatment with T3, and these (biochemical evidence of increased bone resorption or palpitations) arose in studies where the LT4:T3 ratio of treatment was particularly low (4:1) 39,52 .”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [39] source

      Not checked in the free run.

    • cites [52] source

      Not checked in the free run.

  • May combine two claims.

    Findingnone given

    A small number of studies noted increased heart rate in the combination vs monotherapy groups, but the absolute difference in heart rate was small, generally of the order of a few bpm.

    “While a small number of studies noted increased heart rate in the combination vs. monotherapy groups, the absolute difference in heart rate was small, generally of the order of a few bpm.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    The published randomised comparisons of T3+LT4 combinations with LT4 monotherapy employed a wide range of LT4:T3 ratios, from 4:1 to 15:1, and differing patient populations.

    “These studies employed a wide range of LT4:T3 ratios, from 4:1 to 15:1, and differing patient populations, with spontaneously occurring hypothyroidism, or following ablation of thyroid tissue due to thyroidectomy or radioiodine treatment.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Only 27 spontaneous AE reports were received for the four individual AE within the supraventricular arrhythmia category, with one supraventricular arrhythmia reported for each 39,314,895 units of the T3-LT4 combination tablet sold.

    “However, only 27 spontaneous AE reports were received for the four individual AE within this category (see above), with one supraventricular arrhythmia reported for each 39,314,895 units of the T3-LT4 combination tablet sold.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: The number of packs of the T3-T4 combination tablet sold is a valid proxy for patient exposure to the medication.

  • May combine two claims.

    Premisecitation

    The plasma elimination half-lives of LT4 and T3 are about 7.5 and 1.4 days, respectively.

    “The plasma elimination half-lives of LT4 and T3 are about 7.5 and 1.4 days, respectively 29,30 .”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [29] source

      Not checked in the free run.

    • cites [30]

      Not checked in the free run.

  • May combine two claims.

    Interpretationcitation

    Once-daily co-administration of LT4 and T3 in a manner that would provide 24-hour coverage with T3 would likely lead to excessive peak T3 concentrations, although this could be addressed by twice-daily administration.

    “Once-daily co-administration of these hormones (as is the case for LT4 preparations) in a manner that would provide 24-hour coverage with T3 would likely lead to excessive peak T3 concentrations, although this could be addressed by twice-daily administration 31 .”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [31] source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    LT4 is a prodrug for the active thyroid hormone T3, which is generated from LT4 in target tissues by deiodinase enzymes D1 and D2.

    “LT4 is actually a prodrug for the active thyroid hormone, T3, which is generated from LT4 in target tissues by the action of deiodinase enzymes (specifically, deiodinases D1 and D2) 15 .”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [15]

      Not checked in the free run.

  • Classified as probably not a substantial claim. May combine two claims.

    Premisecitation

    Administration of an additional thyroid hormone can lead to overtreatment, with an increased risk of adverse cardiac reactions like atrial fibrillation, and osteoporosis, among other potential adverse outcomes.

    “It is important therefore to establish the safety of T3-T4 combination therapy, to ensure that administration of an additional thyroid hormone does not lead to over treatment, with an increased risk of adverse cardiac reactions like atrial fibrillation, and osteoporosis, among other potential adverse outcomes 5 .”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [5] source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Experimental data from three decades ago suggested that areas of localised hypothyroidism may exist in LT4-treated rodents with hypothyroidism, and addition of T3 to LT4 corrected this situation.

    “In addition, experimental data from three decades ago suggested that areas of”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [18] source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Levels of T3 in people with optimally TSH-treated hypothyroidism tend to be lower than those of the general population without thyroid dysfunction, and it may not be possible to bring T3 back to the usually observed level without suppressing TSH below its reference range.

    “Clinical studies have demonstrated that levels of T3 in people with optimally TSH-treated hypothyroidism tend to be lower than those of the general population without thyroid dysfunction, and it may not be possible to bring T3 back to the usually observed level without suppressing TSH to below its own reference range 16 .”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [16]

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    Current management guidelines support a 3-6 month individualised trial of T3 for patients with residual symptoms on optimised LT4 treatment, which must be conducted by a physician who is expert in the management of thyroid dysfunction, after discussion with the patient.

    “Current management guidelines support a 3-6 month individualised trial of T3 for patients with residual symptoms on optimised LT4 treatment, which must be conducted by a physician who is expert in the management of thyroid dysfunction, after discussion with the patient 19,25 .”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [19] source

      Not checked in the free run.

    • cites [25] source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    There was no correlation between serum TSH and heart rate, suggesting that thyroid hormone treatment was not driving heart rate in these subjects.

    “Moreover, there was no correlation between serum TSH and heart rate, suggesting that thyroid hormone treatment was not driving heart rate in these subjects 56 .”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [56] source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    T3 use was associated with an approximately 2-fold increase in prescriptions of antipsychotic drugs, with the use of these drugs increasing in line with the number of T3 prescriptions.

    “However, T3 use was associated with an approximately 2-fold increase in prescriptions of antipsychotic drugs, with the use of these drugs increasing in line with the number of T3 prescriptions.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [55] source

      Not checked in the free run.

  • May combine two claims.

    Interpretationreasoning

    Overall, the clinical literature provides reassuring evidence of safety, especially given the relatively low ratios of LT4:T3 used in some studies.

    “Overall, the clinical literature provides reassuring evidence of safety, especially given the relatively low ratios of LT4:T3 used in some studies.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    Trials to date were heterogeneous in design, and most (but not all) recruited patients with no rationale for benefit from the treatment.

    “Trials to date were heterogeneous in design, and most (but not all, see above) recruited patients with no rationale for benefit from the treatment; future trials need to be conducted in populations more likely to benefit from intervention with T3, to incorporate sensitive, thyroid-specific measures of quality of life, and with enough participants to ensure sufficient statistical power 64 .”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [64] source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Supraventricular arrhythmias are a well known symptom of thyrotoxicosis.

    “For example, supraventricular arrhythmias are a well known symptom of thyrotoxicosis 58 .”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [58]

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    A steady improvement in QoL (measured using ThyPRO) occurred over time after the switch, with no change in body composition or heart rate.

    “A steady improvement in QoL (measured using ThyPRO, a thyroid specific instrument 57 ) occurred over time after the switch, with no change in body composition or heart rate 56 .”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [56] source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    There was no suggestion in this study of increased risk of side-effects in recipients of T3 relating to the cardiovascular system (no increased risk of cardiovascular disease or atrial fibrillation and no increase in statin prescriptions) or the skeleton (no increased risk of fractures, or use of bisphosphonate drugs).

    “There was no suggestion in this study of increased risk of side-effects in recipients of T3 relating to the cardiovascular system (no increased risk of cardiovascular disease or atrial fibrillation and no increase in statin prescriptions) or the skeleton (no increased risk of fractures, or use of bisphosphonate drugs).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [55] source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Mean TSH was lower in those who received T3 vs. only LT4 (1.1 vs. 2.1 mIU/L), though both mean values were within the usual reference range for TSH.

    “Mean TSH was lower in those who received T3 vs.only LT4 (1.1 vs. 2.1 mIU/L), though both mean values were within the usual reference range for TSH 10 .”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [10] source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Some of the trials noted improvements (or trends towards improvement) in clinical parameters such as diastolic cardiac function, QoL, or lipid profiles.

    “Some of these trials did note improvements (or trends towards improvement) in clinical parameters such as diastolic cardiac function 34 , QoL 36,40,50,51 , or lipid profiles 39,53 .”
    Quote in the paperNot a substantial claim0 of 7 sources checked
    • cites [34]

      Not checked in the free run.

    • cites [36]

      Not checked in the free run.

    • cites [40] source

      Not checked in the free run.

    • cites [50] source

      Not checked in the free run.

    • cites [51] source

      Not checked in the free run.

    • cites [39] source

      Not checked in the free run.

    • cites [53] source

      Not checked in the free run.

  • May combine two claims.

    Study design and conductcitation

    Under reporting of AE and the inclusion of only limited details in submissions of AE was a potential source of bias, and causality cannot always be established with confidence.

    “Under reporting of AE and the inclusion of only limited details in submissions of AE was a potential source of bias, and causality cannot always be established with confidence 6 .”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [6]

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S2 (checkable), S3 (load-bearing).

    Premisenone given

    Currently, expert opinion favours the use of lower T3 content than used in most of the trials described in Table 1.

    “Currently, expert opinion favours the use of lower T3 content than used in most of the trials described in Table 1.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given

    The acquisition of data from eight countries, where large amounts of this preparation were prescribed, was a strength of the analysis.

    “The acquisition of data from eight countries, where large amounts of this preparation were prescribed, was a strength of the analysis.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    Guidelines on the concurrent use of LT4 and T3 from 2012 recommended a ratio of 13-20:1 for the LT4:T3 dosage, with a ratio of 17:1 suggested in updated guidance from 2023.

    “For example, guidelines on the concurrent use of LT4 and T3 from 2012 19,25 recommended a ratio of 13-20:1 for the LT4:T3 dosage, with a ratio of 17:1 suggested in updated guidance from 2023 19 .”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [19] source

      Not checked in the free run.

    • cites [25] source

      Not checked in the free run.

  • May combine two claims.

    Study design and conductreasoning

    A synthesis of the safety of combining LT4 with T3 is limited by the lack of consensus on optimal trial designs and patient populations for evaluating this treatment, as well as the limited evidence base for establishing the optimal LT4:T3 ratio to use clinically.

    “A synthesis of the safety of combining LT4 with T3 is also limited by the lack of consensus on optimal trial designs and patient populations for evaluating this treatment, as well as the limited evidence base for establishing the optimal LT4:T3 ratio to use clinically for people with hypothyroidism.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Study design and conductown data

    The real-world evaluation of the safety of a LT4-T3 combination tablet was retrospective, uncontrolled and based on spontaneous AE reports.

    “Our real-world evaluation of the safety of a LT4-T3 combination tablet was retrospective, uncontrolled and based on spontaneous AE reports.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Study design and conductnone given

    The clinical evidence base is heterogeneous, especially for safety outcomes, which were not given the same priority as efficacy findings in most of the publications reviewed.

    “Also, the clinical evidence base is heterogeneous, especially for safety outcomes, which were not given the same priority as efficacy findings in most of the publications reviewed.”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim. May combine two claims.

    Study design and conductnone given

    This is a narrative, rather than a systematic, review, which is its main limitation, although a structured search strategy was used.

    “This is a narrative, rather than a systematic, review, which is its main limitation, although we did use a structured search strategy, as described above.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Study design and conductcitation

    Spontaneous AE reporting gives no information on the incidence or prevalence of specific AE, although analyses of this type have been useful for exploring potential safety issues with medications, including within the field of thyroid research.

    “Spontaneous AE reporting gives no information on the incidence or prevalence of specific AE, although analyses of this type have been useful for exploring potential safety issues with medications, including within the field of thyroid research 6 .”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [6]

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given

    Availability of data from only some countries was another possible source of bias.

    “Availability of data from only some countries was another possible source of bias.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Guidelines do not support the use of desiccated thyroid extract for this purpose.

    “Guidelines do not support the use of desiccated thyroid extract for this purpose 19,25 .”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [19] source

      Not checked in the free run.

    • cites [25] source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    Recent expert advice provides similar recommendations, which encompasses the physiological ratio of T4:T3 in the circulation.

    “Recent expert advice provides similar recommendations 65 , which encompasses the physiological ratio of T4:T3 in the circulation 66,67 .”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [65] source

      Not checked in the free run.

    • cites [66] source

      Not checked in the free run.

    • cites [67] source

      Not checked in the free run.

33 of 33

  • The paper relies on this without support.

    The number of packs of the T3-T4 combination tablet sold is a valid proxy for patient exposure to the medication.

    “The number of packs of this medication sold in various countries 8 was used to provide context in respect of the numbers of AE reported compared with the amount of medication in circulation.”
    “The numbers of AE were low in each case, despite a relatively high patient exposure, especially considering the total number of single units of the T3-LT4 combination sold in these countries (1,061,502,158) during the time period in which the AE were collected (Jan 2009 to July 2024, see Methods).”

  • The paper relies on this without support.

    The commercial T3-T4 combination tablet (LT4:T3 ratio 5:1) is representative of LT4+T3 combination therapy more generally.

    “This review presents a novel analysis of spontaneously reported AE for a commercial T3-T4 combination tablet (marketed in different countries as Euthyral V R or Novothyral V R ), which contains LT4 and T3 in a ratio of 5:1 (LT4/T3 tablet strengths 100 mcg/20 mcg, or 75 mcg/15 mcg).”
2 of 2

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

Each contradiction between two passages listed here was confirmed by an independent check.

  • Stated trial-ratio range excludes a listed trial

    Minor

    The text says the trials used LT4:T3 ratios from 4:1 to 15:1, but Table 1 lists a trial with a 20:1 ratio. The table also lists ratios of 17:1 and 3.2:1 outside the stated range.

  • Different AE counts have the same per-pack rate

    Minor

    The table defines the per-pack figure as total packs sold divided by the number of adverse events. The blood-disorders and pregnancy rows report 7 and 14 events respectively but give the same per-pack figure.

  • AE analysis alternates between eight and nine countries

    Minor

    The analysis identifies eight countries, but the Table 2 note describes the sales denominator as covering nine countries.

  • Table 1 gives a different publication year for reference 39

    Minor

    Table 1 dates study 39 to 2011, whereas its reference entry gives 2010.

  • AE reporting period has two different start months

    Minor

    The methods specify January 2009 as the start of the period, while the Table 2 caption specifies February 2009.

  • Equal AE counts have different per-pack rates

    Minor

    Both rows report 14 adverse events, so dividing the same total number of packs by those counts should give the same per-pack figure. Table 2 instead gives 326,718 and 233,370.

6 of 6

Cites

Flagged first, then by citations

Research works printed but not linked: 1

  1. Malaty W. Primary hypothyroidism. BMJ Best Practice. 2024 Aug 18 [cited Sep 2024]. Available from https://bestpractice.bmj.com/topics/en-gb/535

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Related

Authors
Gottwald-Hostalek, U., & Tayrouz, Y.
Affiliations
  • Merck Healthcare KGaA
  • Merck Healthcare KGaA, Darmstadt (Germany) (DE)
Venue
Current Medical Research and Opinion
Publisher
Informa UK Limited
Published
2024-12
Volume
40
Issue
12
Pages
2109-2116
ISSN
  • 0300-7995 (ISSN-L)
  • 1473-4877
DOI
10.1080/03007995.2024.2435460
OpenAlex
W4404941483
Semantic Scholar
d630761bfca9e34ba9a3632817061f7fc5bdf35d
Cited by
6
References
62
Citations by year
2026: 3 · 2025: 3
FWCI
0.35
Type
journal article
Language
en
Open access
Licence
Locations
  • Current Medical Research and Opinion (publishedVersion, other-oa)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Disorders and Treatments
  • Health Sciences › Medicine › Surgery › Thyroid and Parathyroid Surgery
  • Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Toxicology › Pharmacovigilance and Adverse Drug Reactions
Keywords
triiodothyronine, levothyroxine, hypothyroidism, combination thyroid hormone therapy, thyrotoxicosis, drug safety, adverse drug reactions, pharmacovigilance, patient-reported outcomes
MeSH terms
Drug Therapy, Combination, Humans, Hypothyroidism, Thyroxine, Triiodothyronine, Randomized Controlled Trials as Topic

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Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

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